Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
This pilot phase II trial studies how well rituximab and latent membrane protein
(LMP)-specific T-cells work in treating pediatric solid organ recipients with Epstein-Barr
virus-positive, cluster of differentiation (CD)20-positive post-transplant
lymphoproliferative disorder. Rituximab is a monoclonal antibody that may interfere with the
ability of cancer cells to grow and spread. LMP-specific T-cells are special immune system
cells trained to recognize proteins found on post-transplant lymphoproliferative disorder
tumor cells if they are infected with Epstein-Barr virus. Giving rituximab and LMP-specific
T-cells may work better in treating pediatric organ recipients with post-transplant
lymphoproliferative disorder than rituximab alone.
Phase
Phase 2
Funding Agency/Sponsor
National Cooperative Group
Disease
Pediatric Cancer
Enrollment Eligibility
Inclusion Criteria:
- Patient must have a history of solid organ transplantation
- Patients must have biopsy-proven newly diagnosed, relapsed or refractory polymorphic
or monomorphic PTLD using the World Health Organization (WHO) classification and that
is:
- CD20 positive
- EBV positive by Epstein-Barr virus early ribonucleic acid (RNA) (EBER) in situ
hybridization (preferred) and/or LMP immunoperoxidase staining
- There must be evaluable disease at study entry either by imaging or by serial
endoscopic biopsies.
- Note: a measurable node must have an LDi (longest diameter) greater than 1.5 cm;
a measurable extranodal lesion should have an LDi greater than 1.0 cm; all tumor
measurements must be recorded in millimeters (or decimal fractions of
centimeters)
- Patients must be considered medically refractory to decreased immunosuppression (50%
or greater reduction) for at least 1 week or there must be documentation in the
medical chart that decreased immunosuppression would be associated with an
unacceptable risk of rejection
- Patients must have a performance status corresponding to Eastern Cooperative Oncology
Group (ECOG) scores of 0 or 1
- Use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years
of age
- Patients must have a life expectancy of >= 8 weeks
- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Myelosuppressive chemotherapy: must not have received within 2 weeks of entry onto
this study
- COHORT A and B: Patient must not have received therapy with anti-CD20 monoclonal
antibodies within 90 days of entry onto this study
- COHORT C: Patient must have received rituximab at 375 mg/m^2 weekly for at least 3
doses within the last 90 days prior to study enrollment
- Must not have received any prior radiation to any sites of measurable disease
- Must not have received any prior stem cell transplant
- Must not have received investigational therapy within 30 days of entry onto this study
- Must not have received prior EBV or LMP-specific T cells within 90 days of entry onto
this study
- Must not have received alemtuzumab or other anti-T-cell antibody therapy within 28
days of entry onto this study
- COHORT C: HLA typing is available and will be submitted at the time of enrollment.
Exclusion Criteria:
- Burkitt morphology
- Central nervous system (CNS) involvement; CNS status must be confirmed by lumbar
puncture
- Note: lumbar puncture can be performed at the time of diagnosis and does not need
to be repeated unless there is a change in neurological status or it was
performed more than 14 days prior to study entry
- Bone marrow involvement (> 25%)
- Note: bone marrow aspiration/biopsy can be performed at the time of diagnosis and
does not need to be repeated unless there is a change in peripheral blood counts
or it was performed more than 14 days prior to study entry
- Fulminant PTLD defined as: fever > 38 degrees Celsius (C), hypotension, and evidence
of multi-organ involvement/failure including two or more of the following:
- Bone marrow (including pancytopenia without any detectable B-cell proliferation)
- Liver (coagulopathy, transaminitis and/or hyperbilirubinemia)
- Lungs (interstitial pneumonitis with or without pleural effusions)
- Gastrointestinal hemorrhage
- Any documented donor-derived PTLD
- Hepatitis B or C serologies consistent with past or current infections because of the
risk of reactivation with rituximab
- Severe and/or symptomatic refractory concurrent infection other than EBV
- Pregnant females are ineligible since there is no available information regarding
human fetal or teratogenic toxicities
- Lactating females are not eligible unless they have agreed not to breastfeed their
infants
- Female patients of childbearing potential are not eligible unless a negative pregnancy
test result has been obtained
- Sexually active patients of reproductive potential are not eligible unless they have
agreed to use an effective contraceptive method for the duration of their study
participation and for 12 months following completion of study therapy.
- All patients and/or their parents or legal guardians must sign a written informed
consent
- All institutional, Food and Drug Administration (FDA), and National Cancer Institute
(NCI) requirements for human studies must be met